An estimated 23 to 25 million Americans--about 18% of women and 6% of men--suffer from migraine pain and migraine-related symptoms.sup.1. Attacks are common, with more than 50% of sufferers experiencing one or more episodes per month.sup.2.
Migraine, a heterogeneous disorder, produces a wide spectrum of pain and associated disabilities, both within and among individual sufferers. The spectrum includes mild pain and no disability in approximately 5-15% of migraine attacks, moderate to severe pain and disability in approximately 60-70% of attacks, and incapacitating pain and total disability in the remaining approximately 25-35% of attacks.sup.3,4.
Recent population-based epidemiological studies in the United States and elsewhere, have found that most people with migraine are not currently consulting a physician for their migraine attacks, and only about one-third have ever been diagnosed by a doctor.sup.5,6,7,8. The overwhelming majority (95% of men and 97% of women) of migraineurs, i.e., individuals who suffer from migraines, used medication to assuage their pain, although only about 28% of the men and 40% of the women have ever used prescription medications.sup.9,10. More than 90% of migraineurs use nonprescription medication for their migraines and the majority use nonprescription medications exclusively.sup.5,11.
Many migraine sufferers use single-agent nonprescription analgesics such as acetaminophen, or aspirin, or nonsteroidal anti-inflammatory agents to treat their attacks.sup.12,13. Despite the widespread use of nonprescription drugs for self-treatment, only prescription drugs are approved for the treatment of migraine in the United States. In other countries, a number of nonprescription drugs are specifically approved for migraine pain.sup.13 ; however, the effectiveness of self-treatment of migraine and the effectiveness of such nonprescription drugs in relieving or aborting migraine pain and/or the characteristic symptoms of migraine has not been adequately studied in well-controlled clinical trials.sup.12,13. Acetaminophen, aspirin and caffeine is approved for relief of nonspecific headaches and tension headaches.sup.15, which are clinical and phsyiologically distinct from migraine. Caffeine is an analgesic adjuvant for a variety of pain conditions and has been included in combination with other analgesics, ergot alkaloids and barbiturates in prescription formulations for migraine.sup.14,16,17,18.
Although the symptom pattern varies among migraine sufferers, the severity of migraine pain justifies a need for vigorous therapy in the great majority of cases. Traditional therapy, such as ergotamine, although effective during prodrome of migraine attack, is known to become progressively less effective if its administration is delayed. Ergotamine is frequently combined with caffeine, a known analgesic adjuvant, to facilitate absorption of the ergot alkaloid. However, repeated dosing of ergotamine induces long-lasting and cumulative vasoconstriction, thereby requiring careful instructions and management of individuals who take oral preparations for migraine attack.
Because of the cumulative toxicity of ergotamine and its derivatives, safer therapeutics for the treatment and prophylaxis of migraine have been sought. Examples of such ergotamine alternatives are ergonovine, propranolol and methysergide; however, significant toxicity also occurs in nearly 40% of the individuals who take these agents. In addition, many of these agents are completely ineffective in the treatment of acute migraine. A prescription antimigrainous medication which is an alternative to ergotamine and its derivatives is sumatriptan (or sumatriptan succinate), which is a selective 5-hydroxytryptamine.sub.1 receptor subtype agonist that is effective in the prodrome phase of a migraine attack.
Thus, a clear goal in the art is to discover new, safe, nontoxic and effective anti-migraine drugs and treatments, particularly nonprescription treatment medications that can be self-administered without the need of a medical prescription.
Until the present invention, the nonprescription combination of acetaminophen, aspirin and caffeine (APAP/ASA/CAF) has not been demonstrated to be a useful treatment for the pain and the symptoms of migraine attack, which is clinically and physiologically considered to be distinct from non-migraine headaches, such as nonspecific headaches or tension headaches. In addition, prior to the present invention, the combination of acetaminophen, aspirin and caffeine (APAP/ASA/CAF) was not discovered to alleviate one or more of the symptoms of migraine, such as nausea, photophobia, phonophobia and functional disabilities. Further, prior to the present invention, the APAP/ASA/CAF combination had not been discovered to abort the prodrome phase of a migraine attack, i.e., the phase prior to migrainous aura and acute migraine pain. Moreover, not until the present invention as described herein was it discovered that a combination of APAP/ASA/CAF efficaciously aborted migraine pain and also significantly reduced the migraine symptoms of nausea, photophobia, phonophobia and functional disabilities. A migraine treatment involving the use of a nonprescription combination of APAP/ASA/CAF in accordance with the present invention promises to have important cost and safety advantages over currently used prescription agents.